Fully chemical gene synthesis

A team of scientists has found a new way to synthesize DNA, bringing us a step closer to creating a functional human genome with epigenetic modifications.

Current methods of gene synthesis rely on enzymes to construct genes and genomes from short nucleic-acid chains or oligonucleotides.

However, enzyme use is not without shortcomings; it’s difficult to automate the process, and epigenetic information — responsible for switching genes on or off — cannot be readily incorporated in the final gene product.

Now, a team co-led by Tom Brown and Ali Tavassoli from the University of Oxford and the University of Southampton are showcasing in a new research in Nature Chemistry1 a fully chemical method of gene synthesis called click-DNA ligation. It relies on a class of fast and simple biocompatible reactions called “click chemistry” to stitch together multiple DNA fragments into a gene.

In their paper, the team creates an epigenetically-modified variant of the gene iLOV, which encodes a green fluorescent protein, by click DNA ligation of 10 oligonucleotides. This new method can incorporate epigenetic information in large DNA constructs, can produce large quantities of a single gene and is amenable to automation.

"Genome synthesis will play an increasingly important role in scientific research. We believe our purely chemical approach has the potential to significantly accelerate efforts in this vitally important area, and ultimately lead to a better understanding of biological systems," says Tavassoli.